Decades of research have provided evidence that Alzheimer's disease (AD) is caused in part by cerebral accumulation of amyloid beta‐protein (Aβ). In 2023, the US Food and Drug Administration gave full regulatory approval to a disease‐modifying Aβ antibody for early AD. Secondary prevention trials with Aβ antibodies are underway. We summarize peer‐reviewed evidence for targeting Aβ and argue that regulators should consider approving new agents working by similar mechanisms (Aβ antibodies and vaccines) based on robust amyloid lowering and reasonable safety. The urgent need to provide treatments to millions of mildly symptomatic patients suggests that AD should join other diseases for which standard approval is based on significant changes in mechanistically meaningful biomarkers coupled with safety. Robust amyloid lowering in secondary prevention trials of people who have amyloid plaques but are asymptomatic could also provide evidence of a change in the pathophysiological progression of AD as a basis for regulatory approval.Highlights Thirteen key findings support amyloid beta as a cause of Alzheimer's disease (AD). Three immunotherapies lower amyloid and slow decline, allowing regulatory approval. New such agents could be considered for approval due to amyloid lowering and safety. Urgency suggests AD may join diseases with approval due to a key biomarker + safety.

中文翻译：

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基于明确生物标志物证据的监管部门批准阿尔茨海默病中降低淀粉样蛋白免疫疗法的案例


数十年的研究提供证据表明，阿尔茨海默病 （AD） 部分是由淀粉样蛋白 β （Aβ） 的脑积累引起的。2023 年，美国食品药品监督管理局 （FDA） 全面批准了一种用于早期 AD 的疾病修饰 Aβ 抗体。使用 Aβ 抗体的二级预防试验正在进行中。我们总结了靶向 Aβ 的同行评审证据，并认为监管机构应考虑基于强大的淀粉样蛋白降低和合理安全性批准通过类似机制（Aβ 抗体和疫苗）起作用的新药物。迫切需要为数百万轻度症状的患者提供治疗，这表明 AD 应该加入其他疾病的行列，这些疾病的标准批准是基于具有机械意义的生物标志物的重大变化和安全性。在对有淀粉样蛋白斑块但无症状的人进行的二级预防试验中，强效降低淀粉样蛋白也可能提供 AD 病理生理进展变化的证据，作为监管批准的依据。亮点 13 项主要发现支持 β 淀粉样蛋白是阿尔茨海默病 （AD） 的一个原因。三种免疫疗法可降低淀粉样蛋白并减缓淀粉样蛋白的下降，从而获得监管部门的批准。由于淀粉样蛋白降低和安全性，可以考虑批准新的此类药物。紧迫性表明，由于关键生物标志物 + 安全性，AD 可能会加入获得批准的疾病。